Cynaropicrin from Cynara scolymus L. suppresses Porphyromonas gingivalis LPS-induced production of inflammatory cytokines in human gingival fibroblasts and RANKL-induced osteoclast differentiation in RAW264.7 cells
Periodontal diseases are a major public health problem affecting over half of the adult population worldwide. Lipopolysaccharide (LPS) produced by the periodontopathic bacterium Porphyromonas gingivalis induces the expression of inflammatory cytokines that promote inflammatory bone destruction. Mounting evidence supports that periodontal diseases are involved in the onset and progression of several systemic diseases, such as aspiration pneumonia and diabetes. Although treatment of periodontal diseases by removing the periodontopathic bacteria by brushing is a standard practice, it has limitations and is not effective in all cases. Therefore, a new method to replace or complement brushing is needed for the treatment of periodontal diseases. In this study, we investigated the anti-inflammatory effects of an extract from Cynara scolymus L. and its pharmacologically effective compound cynaropicrin, a sesquiterpene lactone, on human gingival fibroblasts (HGFs) stimulated by LPS and the potential anti-osteoclastogenic effects on RAW264.7 cells induced by receptor activator of NF-κB ligand (RANKL). We found that cynaropicrin inhibited IL-8 and IL-6 mRNA and protein synthesis in LPS-stimulated HGFs in a dose-dependent manner. P. gingivalis LPS-induced degradation of IκBα and phosphorylation of NF-κB p65 were also suppressed by cynaropicrin, as was LPS-stimulated NF-κB transactivation. Thus, cynaropicrin’s inhibition of P. gingivalis LPS-induced IL-8 and IL-6 expression may be due to the inhibition of the NF-κB pathway. Furthermore, we showed that cynaropicrin dramatically reduced RANKL-induced osteoclast differentiation. These results suggest that cynaropicrin may be useful for preventing periodontal diseases and could prove valuable in the development of more effective preventative approaches for periodontal diseases.
KeywordsCynaropicrin Periodontal diseases Inflammatory cytokine Human gingival fibroblasts Osteoclast differentiation
This work was supported by JSPS KAKENHI, the Dental Research Center, Nihon University School of Dentistry, and the Nihon University Multidisciplinary Research Grant for 2017.
Compliance with ethical standards
Conflict of interest
The authors confirm that there are no conflicts of interests.
- 6.Sjögren P, Nilsson E, Forsell M, Johansson O, Hoogstraate J (2008) A systematic review of the preventive effect of oral hygiene on pneumonia and respiratory tract infection in elderly people in hospitals and nursing homes: effect estimates and methodological quality of randomized controlled trials. J Am Geriatr Soc 56:2124–2130CrossRefGoogle Scholar
- 9.Noorafshan A, Ashkani-Esfahani S (2013) A review of therapeutic effects of curcumin. Curr Pharm Des 19:2032–2046Google Scholar
- 15.Tamura R, Chen Y, Shinozaki M, Arao K, Wang L, Tang W, Hirano S, Ogura H, Mitsui T, Taketani S, Ando M, Kataoka T (2012) Eudesmane-type sesquiterpene lactones inhibit multiple steps in the NF-κB signaling pathway induced by inflammatory cytokines. Bioorg Med Chem Lett 22:207–211CrossRefGoogle Scholar
- 24.Zhou X, Han J, Liu Z, Song Y, Wang Z, Sun Z (2014) Effects of periodontal treatment on lung function and exacerbation frequency in patients with chronic obstructive pulmonary disease and chronic periodontitis: a 2-year pilot randomized controlled trial. J Clin Periodontol 41:564–572CrossRefGoogle Scholar
- 25.Takashiba S, Takigawa M, Takahashi K, Myokai F, Nishimura F, Chihara T, Kurihara H, Nomura Y, Murayama Y (1992) Interleukin-8 is a major neutrophil chemotactic factor derived from cultured human gingival fibroblasts stimulated with interleukin-1β or tumor necrosis factor α. Infect Immun 60:5253–5258Google Scholar
- 26.Bickel M (1993) The role of interleukin-8 in inflammation and mechanisms of regulation. J Periodontol 64:456–460Google Scholar
- 32.Brandolini L, Sergi R, Caselli G, Boraschi D, Locati M, Sozzani S, Bertini R (1997) Interleukin-1β primes interleukin-8-stimulated chemotaxis and elastase release in human neutrophils via its type I receptor. Eur Cytokine Netw 8:173–178Google Scholar